Biomedical subjects

J Guo

Publications and source records attributed to J Guo.

At least 289 records · Page 16Linked to original sources

PubMed1997

Synthesis and pharmacological evaluation of N-(2,5-disubstituted phenyl)-N'-(3-substituted phenyl)-N'-methylguanidines as N-methyl-D-aspartate receptor ion-channel blockers.

In the mammalian central nervous system, the N-methyl-D-aspartate (NMDA) subclass of glutamate receptors may play an important role in brain diseases such as stroke, brain or spinal cord trauma, epilepsy, and certain neurodegenerative diseases. Compounds which specifically antagonize the actions of the neurotransmitter glutamate at the NMDA receptor ion-channel site offer a novel approach to treating these disorders. CERESTAT (4, aptiganel CNS 1102) is currently undergoing clinical trial for the treatment of traumatic brain injury and stroke. Previously, we reported that analogues of N-1-naphthyl-N'-(3-ethylphenyl)-N'-methylguanidine (4) bound to the NMDA receptor ion-channel site with high potency and selectivity. Recently, molecules active at both sigma receptors and NMDA receptor sites were investigated. A series of substituted diphenylguanidines 6 which are structurally related to N-1-naphthyl-N'-(3-ethylphenyl)-N'-methylguanidine was prepared. Compounds containing appropriate substitution pattern in one of the phenyl rings of diphenylguanidines displayed high affinity. For example, N-(2,5-dibromophenyl)-N'-(3-ethylphenyl)-N'- methylguanidine (27b, R2 = R5 = Br, R3 = C2H5) exhibited potency at both sigma receptors and NMDA receptor sites; 27b also showed high efficacy in vivo in a neonatal rat excitotoxicity model. Further studies indicated that substituent effects were important in this compound series, and 2,5-disubstituted phenyl was the preferred substitution pattern for high-affinity binding at NMDA receptor sites. Bromo and methylthio were the optimal substituents for the R2 and R5 positions of the 2,5-disubstituted phenyl group, respectively. N-(2-Bromo-5-(methylthio)phenyl)-N'- (3-ethylphenyl)-N'-methylguanidine (34b, R2 = Br, R5 = SMe, R3 = C2H5) was highly active at NMDA receptor sites. We found that the binding affinity of guanidines of type 6 could be further enhanced with the appropriate substitution at R3. Optimal activity in this series are afforded by 43b and 44b (R2 = Cl or Br, R5 = R3 = SCH3). Both 43b and 44b bound to NMDA receptor sites with high potency and selectivity (Ki vs [3H]MK-801: 1.87 and 1.65 nM, respectively); these compounds are active in vivo in various animal models of neuroprotection. The structure--activity relationships for these compounds at the NMDA receptor ion-channel site are discussed.

Animals↗

PubMed1997

Typing of urinary JC virus DNA offers a novel means of tracing human migrations.

Although polyomavirus JC (JCV) is the proven pathogen of progressive multifocal leukoencephalopathy, the fatal demyelinating disease, this virus is ubiquitous as a usually harmless symbiote among human beings. JCV propagates in the adult kidney and excretes its progeny in urine, from which JCV DNA can readily be recovered. The main mode of transmission of JCV is from parents to children through long cohabitation. In this study, we collected a substantial number of urine samples from native inhabitants of 34 countries in Europe, Africa, and Asia. A 610-bp segment of JCV DNA was amplified from each urine sample, and its DNA sequence was determined. A worldwide phylogenetic tree subsequently constructed revealed the presence of nine subtypes including minor ones. Five subtypes (EU, Af2, B1, SC, and CY) occupied rather large territories that overlapped with each other at their boundaries. The entire Europe, northern Africa, and western Asia were the domain of EU, whereas the domain of Af2 included nearly all of Africa and southwestern Asia all the way to the northeastern edge of India. Partially overlapping domains in Asia were occupied by subtypes B1, SC, and CY. Of particular interest was the recovery of JCV subtypes in a pocket or pockets that were separated by great geographic distances from the main domains of those subtypes. Certain of these pockets can readily be explained by recent migrations of human populations carrying these subtypes. Overall, it appears that JCV genotyping promises to reveal previously unknown human migration routes: ancient as well as recent.

Adult↗

PubMed1997

Chromosome mapping and expression of the human interleukin-13 receptor.

Interleukin-13 (IL-13) is a cytokine secreted by activated T cells and shares most but not all biological activities with interleukin-4 (IL-4). Both cytokines play an important role as a switch factor directing synthesis of IgE; they act on monocytes and endothelial cells, but unlike IL-4, IL-13 does not act on T cells. These cytokines have both common and distinct components in their respective receptors. Based on sequence similarity shared by cytokine receptor family members, we have identified a cDNA encoding the human IL-13 receptor (IL-13R). This cDNA was used to examine the pattern of IL-13R mRNA expression by Northern blot analyses of poly(A)+ RNA purified from different human tissues and cell lines. Among several myeloma cell lines analyzed, the U266 cell line was the only one found to express IL-13R transcripts. This cell line is also the only one described as producing IgE. The IL-13R gene was mapped to chromosome Xq24 by in situ hybridization. Interestingly, this locus is near that of the CD40 ligand gene, the product of which is also involved, like IL-13, in proliferation and IgE isotype switching of human B cells. The human IL-13R gene maps between two cytokine receptor genes located on the chromosome arm Xq region: the interleukin-2 receptor gamma chain gene (Xq13.1) and the interleukin-9 receptor gene (Xq28). The lack of nucleotide sequence similarity suggests unrelated evolutionary pathways between these receptor genes.

Amino Acid Sequence↗

PubMed1997

Urine and urine-derived compounds induce c-fos mRNA expression in accessory olfactory bulb.

Soiled bedding from male mice induced c-fos mRNA expression in the accessory olfactory bulb (AOB) and main olfactory bulb (MOB) of female mice. The increase observed in the AOB, but not the MOB, was dependent on the presence of the vomeronasal organ (VNO). Male urine alone also increased c-fos mRNA expression in the AOB. The urine-derived compounds dehydro-exo-brevicomin (DHB) and sec-butyl-dihydrothiazole (SBT) in combination with major urinary protein (MUP) induced significantly greater c-fos mRNA expression in the AOB than in the MOB. The results indicate that compounds derived from male urine are detected at the AOB and suggest that specific urinary compounds play an important role in AOB-mediated reproductive events.

Alpha-Globulins↗

PubMed1997

Mutations in the second cytoplasmic loop of the rat parathyroid hormone (PTH)/PTH-related protein receptor result in selective loss of PTH-stimulated phospholipase C activity.

To define the structural requirements of the parathyroid hormone (PTH)/PTH-related protein (PTHrP) receptor necessary for activation of phospholipase C (PLC), receptors with random mutations in their second cytoplasmic loop were synthesized, and their properties were assessed. A mutant in which the wild type (WT) rat PTH/PTHrP receptor sequence EKKY (amino acids 317-320) was replaced with DSEL had little or no PTH-stimulated PLC activity when expressed transiently in COS-7 cells, but it retained full capacity to bind ligand and to generate cAMP. This phenotype was confirmed in LLC-PK1 cells stably expressing the DSEL mutant receptor, where both PTH-stimulated PLC activity and sodium-dependent phosphate co-transport were essentially abolished. Individual mutations of these four residues point to a critical role for Lys-319 in receptor-G protein coupling. PTH-generated IPs were reduced to 27 +/- 13% when K319E, compared with the WT receptor, and PLC activation was fully recovered in a receptor revertant in which Glu-319 in the DSEL mutant cassette was restored to the WT residue, Lys. Moreover, the WT receptor and a mutant receptor in which K319R had indistinguishable properties, thus suggesting that a basic amino acid at this position may be important for PLC activation. All of these receptors had unimpaired capacity to bind ligand and to generate cAMP. To ensure adequacy of Galphaq-subunits for transducing the receptor signal, Galphaq was expressed in HEK293 and in LLC-PK1 cells together with either WT receptors or receptors with the DSEL mutant cassette. PTH generated no inositol phosphates (IPs) in either HEK293 or LLC-PK1 cells, when they expressed DSEL mutant receptors together with Galphaq. In contrast, PTH generated 2- and 2. 5-fold increases in IPs, respectively, when these cells co-expressed both the WT receptor and Galphaq. Thus, generation of IPs by the activated PTH/PTHrP receptor can be selectively abolished without affecting its capacity to generate cAMP, and Lys-319 in the second intracellular loop is critical for activating the PLC pathway. Moreover, alpha-subunits of the Gq family, rather than betagamma-subunits, transduce the signal from the activated receptor to PLC, and the PLC, rather than the adenylyl cyclase, pathway mediates sodium-dependent phosphate co-transport in LLC-PK1 cells.

Amino Acid Sequence↗

PubMed1997

Transgenic mice overexpressing human c-mpl ligand exhibit chronic thrombocytosis and display enhanced recovery from 5-fluorouracil or antiplatelet serum treatment.

The consequences of long-term in vivo expression of human c-mpl ligand in a mouse model were examined. Transgenic mice expressing the human full-length cDNA in the liver exhibited a fourfold increase in circulating platelet count that persisted stably over the life of the animals. Transgenic animals thrived and appeared healthy for at least 500 days. Transgenic platelets appeared normal with respect to surface antigens and response to platelet aggregation agonists. The highest-expressing transgenic line maintained human c-mpl ligand serum levels of 3 ng/mL. Megakaryocyte numbers in bone marrow and spleen were elevated, as were bone marrow and spleen megakaryocyte colony-forming cells (MEG-CFC). Megakaryocytes were observed in the bone marrow, spleen, liver, and lung, but in no other sites. Circulating myeloid and lymphoid cell populations were increased twofold. Additionally, the animals had a slight but significant anemia despite an increase in marrow colony-forming units-erythroid (CFU-E). No evidence of myelofibrosis was observed in the bone marrow. The platelet nadir in response to administration of either antiplatelet serum (APS) or 5-fluorouracil (5FU) was significantly reduced relative to the control level. Furthermore, the red blood cell (RBC) nadir was reduced relative to control levels in both models, suggesting that c-mpl ligand can directly or indirectly support the maintenance of erythrocyte levels following thrombopoietic insult.

Animals↗

PubMed1997

Zinc site redesign in T4 gene 32 protein: structure and stability of cobalt(II) complexes formed by wild-type and metal ligand substitution mutants.

Phage T4 gene 32 protein (gp32) is a zinc metalloprotein which binds cooperatively and preferentially to single-stranded nucleic acids and functions as a replication and recombination accessory protein. Zn(II) coordination by gp32 employs a His-Cys3 metal ligand donor set derived from the His64-X12-Cys77-X9-Cys87-X2-Cys90 sequence in the ssDNA-binding core domain of the molecule. Crystallographic studies reveal that His64 and Cys77 are derived from two independent beta-strands within a distorted three-stranded beta-sheet and are relatively more buried from solvent than are Cys87 and Cys90, which are positioned immediately before and within, respectively, an alpha-helix. In an effort to understand the origin of the stability of the metal complex, we have employed an anaerobic optical spectroscopic, competitive metal binding assay to determine the coordination geometry and association constants (Ka) for the binding of Co(II) to wild-type gp32 and a series of zinc ligand substitution mutants. At pH 7.5, 25 degrees C, wild-type gp32 binds Co(II) with a Ka approximately 1 x 10(9) M-1. Competition experiments reveal that Ka for Zn(II) is 3.0 (+/-1.0) x 10(11) M-1. We find that all non-native metal complexes retain tetrahedral or distorted tetrahedral coordination geometry but are greatly destabilized in a manner essentially of whether a new protein-derived coordination bond is formed (e.g., in H64C gp32) or not. Co(II) binding isotherms obtained for three His64 substitution mutants, H64C, H64D, and H64N gp32s, suggest that each mutant forms a dimeric Cys4 tetrathiolate intermediate complex at limiting [Co(II)]f, each then rearranges at high [Co(II)]f to form a monomolecular site of the expected geometry and Ka approximately 1 x 10(4) M-1. Like the His64 mutants, C77A gp32 appears to form at least two types of complexes over the course of a Co(II) titration: one with octahedral coordination geometry formed at low [Co(II)]f, with a second tetrahedral or five-coordinate site formed at higher [Co(II)]f. Apo C87S and C90A gp32s, in contrast, each form a single complex at all [Co(II)]f, consistent with Cys2-His-H2O tetrahedral geometry of Ka approximately (1-2) x 10(5) M-1. These studies reveal that the local protein structure restricts accommodation of a non-native metal complex in a ligand-specific manner. The implications of this work for de novo design of zinc complexes in proteins are discussed.

Bacteriophage T4↗

PubMed1997

RAB GTPases expressed in human melanoma cells.

The expression of small GTP-binding protein genes of the ras superfamily was examined in pigmented human melanoma cells by a PCR-based strategy. Twenty six different partial cDNA sequences were isolated, including 17 members of the rab subfamily, of which 9 represented novel genes. Some rabs expressed in melanoma cells overlapped with those of platelets: this should prove relevant to the investigation of murine and human disorders characterized by the combination of pigment dilution and a platelet storage pool defect.

Amino Acid Sequence↗

PubMed1997

Cloning and characterization of human homologue of Drosophila retinal degeneration B: a candidate gene for degenerative retinal diseases.

Mutations in the Drosophila retinal degeneration B (D-rdgB) gene cause light-enhanced retinal degeneration. Here, we report the isolation of the cDNA encoding human homologue of the D-rdgB and initial characterization of the gene products. Like D-rdgB, the human rdgB homologue (H-rdgB) is a transmembrane protein with the N-terminus sharing high homology to two closely related cytosolic proteins, phosphatidylinositol transfer protein (PITP) alpha and beta, indicating that rdgB like proteins belong to the family of PITP proteins. Using Northern and Western blotting, we demonstrated that the rdgB homologue is expressed in rat retina, olfactory bulb, and brain, but not in nonneuronal tissues. In the rat retina, immunoreactivity of the rdgB homologue was observed in photoreceptors and throughout the inner nuclear and plexiform layers; the strongest staining was in the inner plexiform layer. In the photoreceptor cells, the rdgB homologue was located primarily in the inner segment where sorting and traffic of membranes required for outer segment assembly take place. These data, together with recent findings showing PITPs as on important component of intracellular membrane traffic apparatus in mammalian cells, suggest that rdgB homologue may play a role in photoreceptor membrane renewal and in neurotransmitter release. Furthermore, using somatic hybrid cell hybridization and fluorescence in situ hybridization H-rdgB gene was mapped to human chromosome 11q13, a region known to contain several retinopathy loci, including Best disease and Bardet-Biedl syndrome I. Therefore, H-rdgB gene is an attractive candidate for several inherited retinal degenerative diseases.

Amino Acid Sequence↗

PubMed1997

Molecular cloning and characterization of rab27a and rab27b, novel human rab proteins shared by melanocytes and platelets.

Rabs are prenylated, membrane-bound proteins involved in vesicular fusion and trafficking. We isolated the complete cDNAs of two rab isoforms, rab27a and rab27b, from human melanoma cells and melanocytes, Rab27a is the human homolog of a rat megakaryocyte rab called ram p25. Rab27b corresponds to a small GTP-binding protein, c25KG, which was previously purified from platelets but whose cDNA had not been cloned. Sequence comparisons with known rabs indicate that rab27a and rab27b comprise a melanocyte/platelet subfamily within the rab family. In addition, rab27a was expressed in a large variety of cell and tissue types, excluding brain, and rab27b manifested itself primarily in testis. Bacterially expressed and purified rab27a and rab27b exhibited GTP-binding activity and can now be used for antibody production and studies of the substrate specificities of geranylgeranyl transferase. In addition, the expression of rab27a and rab27b in both melanocytes and platelets makes them candidates for involvement in mouse and human disorders characterized by the combination of pigment dilution and a platelet storage pool defect.

Amino Acid Sequence↗

PubMed1997

Thyroid peroxidase autoantibodies of IgE class in thyroid autoimmunity.

Recently, we converted a thyroid peroxidase (TPO)-specific human autoantibody Fab (SP1.4) into an IgE molecule (IgE-SP1.4) which permits antigen capture via Fc epsilon receptors on B cells and presentation to T cells. An important question which arose was whether IgE class TPO autoantibodies are present in vivo. By ELISA, TPO autoantibodies of IgG1 and IgG4 subclasses, but not IgE, were readily detectable in patients' sera. However, such negative data were not definitive because high concentrations of IgG class TPO autoantibodies could obscure the presence of much lower concentrations of IgE class autoantibodies. We, therefore, established a specific assay based on IgE "capture" to remove other isotypes before incubation with TPO. In an initial survey, 125I-TPO binding was higher in sera from 16 patients with autoimmune thyroid disease than in 6 controls (8.4 +/- 0.8% versus 0.7 +/- 0.2%; mean +/- SEM). Unlabeled TPO (10(-8) M) inhibited 125I-TPO binding by patients' (but not controls') IgE. Further, TPO binding by IgE-SP1.4 was unaffected by IgG class TPO autoantibodies. Titers of IgE class TPO autoantibodies were low, detectable at a 1/60 dilution in 4/5 sera studied. In a larger series, IgE class TPO autoantibodies were present in 13 of 18 Graves' and in 12 of 17 Hashimoto patients (sera diluted 1/6). Sera were considered to be positive with TPO binding greater than the mean + 3 SD of values for 23 control sera (1.8%). In conclusion, we provide the first evidence for TPO autoantibodies of IgE class in patients with autoimmune thyroid disease. Because of their low concentration, these autoantibodies are unlikely to play a role in antigen presentation in vivo. However, their presence strengthens the link between autoimmune thyroid disease and immune responses involving TH2 cells.

Autoantibodies↗

PubMed1997

The epitopic "fingerprint" of thyroid peroxidase-specific Fab isolated from a patient's thyroid gland by the combinatorial library approach resembles that of autoantibodies in the donor's serum.

A new thyroid peroxidase (TPO)-specific Fab (KM1) was obtained from an immunoglobulin gene combinatorial library of patient KM containing L chain genes amplified with a single "promiscuous" V kappa oligonucleotide primer. The KM1 L chain is encoded by a mutated B3 gene (V kappa IV family). Another mutated B3 L chain had been identified previously in a TPO-specific Fab (WR1.223) isolated from a different patient (WR). In contrast to patient KM, the WR L chains were amplified with a panel of V kappa family-specific primers. Both KM1 and WR1.223 bind TPO with high affinity (approximately 1 x 10(-9) M) and interact with an epitope in the B domain of the TPO immunodominant region. TPO-specific Fab previously isolated from a WR combinatorial library constructed with the promiscuous V kappa primer recognised the TPO A domain and none used a B3-like L chain. Remarkably, for both patients, Fab isolated from L chains generated with the promiscuous V kappa primer had epitopic profiles similar to autoantibodies in the donor's serum (KM-B domain; WR-A domain). Our data indicate that the promiscuous primer preferentially amplifies the dominant L chain present in vivo. However, to obtain a relatively rare Fab (such as the B domain Fab from WR), family-specific kappa primers are required. These findings provide insight into the relationship between TPO autoantibody gene usage, epitopic recognition, and the effectiveness of the combinatorial library approach.

Amino Acid Sequence↗

PubMed1997

Development of bone marrow eosinophilia in mice induced by Aspergillus fumigatus antigens.

A model of allergic bronchopulmonary aspergillosis (ABPA) developed by exposing mice to Aspergillus fumigatus antigen (Af) exhibits peripheral blood (PB), lung, and bone marrow (BM) eosinophilia. Because the BM is a site of eosinophilopoiesis, we have investigated the role of Af in the induction of this process in the BM. Groups of mice were exposed intranasally (i.n.) or intraperitoneally (i.p.) to Af. BM cells from mice were cultured with either Af or allogenic spleen cell supernatant stimulated with Af. Eosinophil counts in different lymphoid compartments, eosinophil peroxidase (EPO), and mRNA for cytokines and IgE in BM cells were studied. Results indicate that the eosinophil numbers were significantly elevated in PB and BM of all Af-exposed mice. Lung lavage eosinophils increased only in the i.n. group. Af induced EPO activity only in BM cultures from Af-exposed mice. The EPO activity was further enhanced by supernatants from spleen cells from Af-exposed mice. mRNA transcription of IL-3 and IL-5 were measurable in BM cells of the ip exposed mice. These findings suggest that Af mediates eosinophil development in BM of mice and this process is promoted by hematopoietic factors generated within the BM and in other lymphoid tissue such as the spleen.

Animals↗

PubMed1997

The sustained inward current in sino-atrial node cells of guinea-pig heart.

Single myocytes were dissociated from the sino-atrial (SA) node of guinea-pig hearts. Only a quite small fraction of the cell population showed spontaneous action potentials and these cells were characterized by the presence of the hyperpolarization-activated cation current If , the delayed rectifier K+ current IK and the L-type Ca2+ current ICa,L as well as by the absence of both the transient outward current Ito and the inward rectifier K+ current IK, 1. After blocking If and IK, depolarizing pulses from -80 mV revealed a large nicardipine-sensitive late current (NSLC). The NSLC was scarcely affected by decreasing extracellular [Ca2+] ([Ca2+]o) from 1.8 to 0.1 mM, while it was decreased significantly by depleting [Na+]o, differently from ICa,L. NSLC was blocked by nicardipine and was increased by Bay K 8644. NSLC was increased by isoprenaline and the additional application of acetylcholine reversed the increase of this current. We conclude that NSLC is largely composed of Ist described in the rabbit SA node pacemaker cells, and that Ist is unique for the pacemaker cells in mammalian SA node cells. Most of the quiescent cells showed neither If nor Ist.

Animals↗

PubMed1997

Immunopathologic responses to Aspergillus antigen in interleukin-4 knockout mice.

Two strains of interleukin-4 (IL-4) gene knockout mice were studied and compared with wild strains to determine the role of IL-4 in the immunopathogenesis of murine allergic aspergillosis. Animals immunized intraperitoneally were subsequently challenged with Aspergillus antigen intranasally. The animals were evaluated for total serum immunoglobulin E (IgE) levels, Aspergillus-specific IgG antibody isotypes, peripheral blood eosinophils, cytokine and chemokine mRNA transcripts in spleen cells, and pulmonary histology. No serum IgE was detected in animals deficient in the IL-4 gene. Aspergillus-specific IgG1 was detected in all animals, while enhanced levels of IgG2a were detected in IL-4 knockout animals challenged with A. fumigatus antigen. There were no differences in the peripheral blood or lung eosinophils in the two groups of mice exposed to A. fumigatus. These results indicate that lung injury in Aspergillus-antigen challenged animals may be the result of the eosinophil mediators and that IgE-mediated injury may not be significant in this model, which may be a significant variation between the model and human allergic aspergillosis.

Animals↗

PubMed1997

Inhibition of LPS-induced TNF-alpha production by calcitonin gene-related peptide (CGRP) in cultured mouse peritoneal macrophages.

The purpose of this study was to examine whether rCGRP has effects on TNF-alpha produced by mouse resident peritoneal macrophages. Macrophages were obtained from the peritoneal exudate of male Balb/c mouse. The cells were plated on culture dishes at a density of 2.5x10(5) cells per well and allowed to adhere for 2 hr. Pretreatment with rCGRP (10 nM-1 microM) for 24 hr, the macrophages were cultured with LPS 1 microg/ml for another 24 h. The medium was harvested for measuring TNF-alpha by ELISA kits. The results showed that rCGRP had no direct effects on TNF-alpha production, but it inhibited LPS-induced TNF-alpha production in a concentration-dependent manner. When rCGRP was at a concentration of 1 microM, the LPS-induced TNF-alpha production was inhibited by 39%. The effect of rCGRP was reversed by hCGRP(8-37) (10 microM), an antagonist of CGRP1 receptor. The LPS-induced TNF-alpha production from macrophages was also inhibited by forskolin 3 microM, an activator of adenylate cyclase. Furthermore, pretreatment with H-89 1 microM or Rp-cAMPS 100 microM, the inhibitors of cAMP-dependent protein kinase, the effect of rCGRP was abolished. These data suggest that the LPS-induced TNF-alpha production is inhibited by rCGRP via activation of cAMP responses in mouse resident peritoneal macrophages.

1-Methyl-3-isobutylxanthine↗

PubMed1997

Facilitation of AVP(4-8) on gene expression of BDNF and NGF in rat brain.

In situ hybridization and Northern blot assay were used to evaluate the effects of exogenous AVP(4-8) on the transcription of mRNAs for nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT-3) in the adult rat brain. NGF and BDNF expression was found to be significantly enhanced by AVP(4-8) administration in the cerebral cortex and hippocampus, but NT-3 expression was not changed. In the same conditions, behavior-active arginine-vasopressin (AVP) showed a small effect and its behavior-inactive homologue, oxytocin did not. Our results suggest that selective regulation of neurotrophin gene expression by the peptides may be responsible for its memory-enhancing function.

Animals↗

PubMed1997

Early failure of the porous coated anatomic cemented unicompartmental knee arthroplasty. Aids to diagnosis and revision.

Unicompartmental knee arthroplasty (UKA) is performed less frequently than total (tricompartmental) knee arthroplasty (TKA). This study examined the range of presenting symptoms and usefulness of diagnostic tests to determine the failure mode; the outcome of surgical revision of failed UKA is also reported. From a consecutive prospective series of 43 Porous Coated Anatomic (Howmedica, Rutherford, NJ) UKAs performed between 1985 and 1992 and followed for an average of 64 months, 12 cases have come to revision surgery (28%). The average time to failure was 37 months. Symptoms preceded revision surgery by an average of 10 months. The most common presenting symptom was pain (100%), followed by swelling (92%), reduced range of motion (42%), instability (42%), and clicking (17%). Failure was caused by polyethylene wear in 50%, loosening of the femoral component in 42%, and progression of patellofemoral arthritis in one patient. The combination of single leg standing anteroposterior radiographs and supine lateral radiographs detected most causes of UKA failure. A bone scan was confirmatory in every case of suspected loosening of the femoral component. Arthroscopy diagnosed polyethylene wear in two cases and progression of joint arthritis in one case and was not helpful in one case. Revision surgery was done with primary TKA components, and follow-up periods averaged 27 months. Bone stock deficiency was found in 58%, but required bone-grafting in only one case. Revision surgery successfully restored pain-free function and range of motion in all cases. Two-year postrevision Hospital for Special Surgery scores are equal to those for primary TKA. Survivorship analysis showed a 33% failure rate at 57 months after Porous Coated Anatomic UKA when revision was the endpoint and a 41% failure rate when unsatisfactory clinical status was the endpoint. Regular follow-up evaluation is suggested for the Porous Coated Anatomic UKA.

Aged↗